Objective: To explore the feasibility of targeted magnetic resonance imaging (MRI)on visualizing tenascin-C (TN-C) expression in atherosclerotic plaque in high-fat diet fed ApoE(-/-) mice.
Methods: Aorta artery atherosclerosis was induced in high fat diet fed ApoE(-/-) mice. The atherosclerotic plaques were observed by 7.0T micro-MRI after 14 weeks. Specimens of the samples were obtained randomly and stained with HE and oil red O to observe the pathological changes. The plaques were stained with anti-TN-C antibody to detecting the TN-C. Targeted probe (anti-TN-C-USPIO) was synthesized through chemical coupling methods. The experimental group was injected with targeted probe through tail vein (10 mgFe/kg), and USPIO was used as controls. MRI was performed 8 hours thereafter, intima signal changing in abdominal aorta was observed; specimens of abdominal aorta were taken after scanning, and were stained by Perl's Prussian blue, the deposition of iron particles was observed.
Results: Compared with baseline level, MRI evidenced thickened aorta wall; signal was enhanced on T1WI and PDWI, but weakened on T2WI after 14 weeks. HE stained tissue samples demonstrated thicker intima. The plaque was confirmed by the oil red O staining. Immunohistochemistry staining showed significantly upregulated TN-C expression in the plaque. Compared to pre-injection status, MRI signal was lost on T2WI in the atherosclerotic lesions at 8 hours after anti-TNC-USPIO injection (ΔOD =4.78±1.41, t=9.59, P<0.05), while T2WI remained unchanged in control group (ΔOD =1.45±1.01, t=1.93, P>0.05) and matched Perl's Prussian stained section showed enriched blue particles deposition within the plaque while there were only scarce blue particles deposition in the control group.
Conclusion: Our results show that targeted MRI is feasible to detect TN-C expression in the plaque in vivo, this method might be used to detect in vivo atherosclerotic plaque in large animals or in humans in the future.